The majority of registry studies on atopic dermatitis include only patients and diagnoses from specialized healthcare. The aim of this retrospective, real-world cohort study was to evaluate the effect of atopic dermatitis severity on comorbidities and total morbidity, with comprehensive data from both primary and specialty healthcare registries covering the entire Finnish adult population. In total, 124,038 patients were identified (median age 46 years; 68% female) and stratified by disease severity. All regression analyses (median follow-up 7.0 years) were adjusted at a minimum for age, sex, obesity, and educational level. Compared with mild atopic dermatitis, severe atopic dermatitis was significantly associated with multiple morbidities, including neurotic, stress-related and somatoform disorders, abscesses, erysipelas/cellulitis, impetigo, herpes zoster, extragenital herpes, bacterial conjunctivitis, septicaemia, lymphomas, alopecia areata, urticaria, other dermatitis, contact allergy, osteoporosis, and intervertebral disc disorders (p < 0.001). In addition, there were significant associations with alcohol dependence, depression, condylomas, rosacea, migraine, sleep apnoea, hypertension, enthesopathies, atherosclerosis, and drug-induced cataract (p < 0.05). Odds ratios were modest and mostly were between 1.10 and 2.75. Furthermore, patients with severe atopic dermatitis had lower incidences of prostate cancer, cystitis, and anogenital herpes than patients with mild atopic dermatitis (p < 0.05). These results suggest that severe atopic dermatitis results in significant overall morbidity.